Mast cells play an important role in many inflammatory and immunological reactions by releasing an array of mediators. The goal of our studies is to understand the intracellular signal transduction pathways that lead to the release of these molecules. In previous studies we observed that protein tyrosine phosphorylation is an early and critical signal for FceRI induced degranulation. The protein tyrosine kinase Syk was found to be tyrosine phosphorylated and activated after receptor aggregation. Syk was also shown to be essential for the receptor-induced release of inflammatory mediators. Recent studies demonstrated that the linker region of Syk plays an important role in regulating its function. Studies also defined the mechanisms for the down regulation of signaling in cells by several mechanisms including the degradation of proteins that are activated and by interaction of regulatory and signaling molecules.